The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dr. Mbah Anthony Uche, University Of Nigeria Teaching Hospital
ClinicalTrials.gov Identifier:
NCT01409837
First received: August 2, 2011
Last updated: September 21, 2013
Last verified: September 2013
  Purpose

This study was conceived in order to explain what the investigators previously observed suggesting that lisinopril, a drug normally used to treat patients with high blood pressure and heart failure, may be effective in treating infertile men with low sperm count. The investigators hypothesized, therefore, that the drug will not only improve sperm quantity and quality but also increase the fertility in such patients. The investigators first of all reviewed the results of previously published investigations and found out that there was only a few previous studies done in humans.with this class of drugs. Besides, the methods used in conducting most of those studies have been so faulted that the results cannot be trusted to be showing the true picture. The investigators looked at the various faults pointed out with respect to the their design and conduct and took care of them while designing the investigators own study. This was an attempt to provide more credible answers to the question of whether lisinopril, and possibly other drugs of similar mode of action, can be useful in rectifying the problem of infertility caused by low sperm count and , if so, whether it will be safe to use it in people who do not have high blood pressure or heart failure. In order to achieve this the investigators studied 33 patients with sperm of low cell concentration, low percentage of motile cells and high percentage of abnormal cells from no known cause. The patients were randomly allocated to receive either lisinopril 2.5mg daily (17 patients) or daily placebo (16 patients)and their sperm characteristics were examined at intervals, starting from the beginning of the study until when it ended 282 weeks later. The patients were also monitored for adverse events throughout the period. The data form all the patients that took part in the random allocation of treatments at the beginning of the study were included in the analysis that followed, irrespective of whether they completed the study or not.


Condition Intervention Phase
Oligospermia
Drug: Lisinopril
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 5-year Prospective, Placebo-controlled, Crossover Evaluation of the Efficacy and Tolerability of Low-dose Lisinopril in Normotensives With Idiopathic Oligospermic Infertility

Resource links provided by NLM:


Further study details as provided by University Of Nigeria Teaching Hospital:

Primary Outcome Measures:
  • Changes From Baseline in the Seminal Fluid Characteristics Throughout the Study [ Time Frame: Week 96. ] [ Designated as safety issue: No ]
    The seminal fluid characteristics were assessed twice before the entry of each patient and both at least two-weeks apart. The two values were averaged and recorded as baseline for week 0 while subsequent changes from the baseline were monitored during each of the scheduled visits at weeks 6, 12, 24, 48, 96, 102, 114, 138, 186 and 282. The two groups swopped treatments at the 96th week. The number of pregnancies achieved was also documented throughout the study period.

  • Total Sperm Cell Count Per Milliliter of Seminal Fluid. [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    the number of sperm cells counted per milliliter volume of seminal fluid

  • Proportion of Sperm Cells With Normal Motility (%) [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    This was determined as the proportion (percent) of the total sperm cells exhibiting both rhythmic and propulsive movements considered to be of normal intensity.

  • Proportion of Sperm Cells With Abnormal Morphology (%) [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Proportion (per cent) of sperm cells with abnormal appearance

  • Ejaculate Volume [ Time Frame: Week 282 ] [ Designated as safety issue: No ]
    The volume in milliliters of seminal fluid produced per ejaculation.

  • Total Sperm Cell Count [ Time Frame: Week 282 ] [ Designated as safety issue: No ]
    The total number of sperm cells found in each milliliter of seminal fluid.

  • Proportion of Sperm Cells With Normal Motility (%) [ Time Frame: Week 282 ] [ Designated as safety issue: No ]
    The proportion (per cent) of the sperm cells exhibiting both rhythmic and propulsive movements considered to be of normal intensity.

  • Proportion of Sperm Cells With Abnormal Morphology (%) [ Time Frame: Week 282 ] [ Designated as safety issue: No ]
    The proportion (per cent) of the total number of sperm cell with abnormal appearance.


Secondary Outcome Measures:
  • Adverse Events Monitoring [ Time Frame: At weeks 6, 12, 24, 48, 96, 102, 114,138, 186 and 282 ] [ Designated as safety issue: Yes ]
    The patients were encouraged to report every event promptly by phone to one of the authors (NOG), no matter however minor.Blood pressure measurements were done with mercury sphygmomanometers fitted with adult-size cuffs (Accoson, England). Serum potassium levels were estimated using the flame photometric method as described by Davidson and Henry


Enrollment: 33
Study Start Date: March 1998
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar pill
Started with Placebo until the crossover.
Experimental: Lisinopril
Started with Lisinopril until the crossover
Drug: Lisinopril
The two groups of patients, A and B, were randomly allocated treatments in a double-blind fashion. Group A was started on the coded drug "DY1" while group B was started on the coded drug "DZ2". Both "DY1" and "DZ2" were very identical in appearance. At week 96 the drugs were swopped between the groups such that group A changed to drug "DZ2" while group B changed to drug "DY1". There was no intervening washout period. The codes were concealed until after the data analysis.
Other Name: (Zestril®, AstraZeneca Pharmaceuticals,Washington NC, USA)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   24 Years to 34 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

The subjects for this investigation were selected from a volunteer pool of male patients attending the fertility clinic of University of Nigeria Teaching Hospital, Enugu. The criteria for their selection were:

Inclusion criteria:

  • regular attendance and on treatment for low sperm count or oligospermia in the fertility clinic for at least 2 years
  • total sperm count at selection from 5 million/ml to 10 million/ml,
  • white blood cell (WBC) count less than 1 million per ml of the ejaculate
  • evidence of undergone comprehensive investigations to exclude secondary causes of low sperm count, (e) evidence of comprehensive investigations to exclude female factor infertility in the spouse
  • an assurance of a personal commitment to continue participating in the study until the end-point was reached and (g) normal blood pressure.

Exclusion criteria:

  • Patients who did not give their consent to participate
  • did not meet the diagnostic criteria for oligospermia at the time of recruitment
  • failed to fulfill any of the above inclusion criteria, even if the diagnostic criteria are fulfilled.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01409837

Locations
Nigeria
University of Nigeria Teaching Hospital, Ituku-Ozalla,
Enugu, Nigeria, 01129
Sponsors and Collaborators
University Of Nigeria Teaching Hospital
Investigators
Principal Investigator: Anthony U Mbah, MD, FMCP University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu
  More Information

Publications:
Mbah AU. Normogonadotrophic, non-obstructive azoospermia: successful treatment of two cases using low-dose lisinopril (Abstract): 24th Annual Scientific Conference of the Association of Physicians of Nigeria. Port Harcourt, 1999.
World Health Organization, WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interactions. 4th ed. Cambridge, United Kingdom: Cambridge University Press; 1999.
39. Lee KC. Fertility treatments and the cost of a healthy baby. Nurs Womens Health. 2011 Feb-Mar;15(1):15-8.
Lee KC. Fertility treatments and the cost of a healthy baby. Nurs Womens Health. 2011 Feb-Mar;15(1):15-8.
Khabibulina MM. [Evaluation of long-term therapy influence with angiotensin converting enzyme inhibitor lisinopril on morphofunctional parameters of the left ventricle, peripheral artery endothelium disfunction and painless myocardial ischemia in premenopausal women with hypertension]. Kardiologiia. 2010;50(1):16-21.
Sangole NV, Dadkar VN. Adverse drug reaction monitoring with angiotensin converting enzyme inhibitors: A prospective, randomized, open-label, comparative study. Indian J Pharmacol. 2010 Feb;42(1):27-31.

Responsible Party: Dr. Mbah Anthony Uche, Dr., University Of Nigeria Teaching Hospital
ClinicalTrials.gov Identifier: NCT01409837     History of Changes
Other Study ID Numbers: GHF/GrS/99/S.3
Study First Received: August 2, 2011
Results First Received: June 22, 2013
Last Updated: September 21, 2013
Health Authority: Nigeria: The National Agency for Food and Drug Administration and Control

Keywords provided by University Of Nigeria Teaching Hospital:
Oligospermia
Male infertility
Lisinopril

Additional relevant MeSH terms:
Infertility
Oligospermia
Genital Diseases, Male
Genital Diseases, Female
Infertility, Male
Lisinopril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014